Medical Parasitology PDF

Access Provided by: Jawetz, Melnick, & Adelberg's Medical Microbiology, 28e Chapter 46: Medical Parasitology INTRODUCTION It is often not appreciated that paras...

Access Provided by: Jawetz, Melnick, & Adelberg's Medical Microbiology, 28e Chapter 46: Medical Parasitology INTRODUCTION It is often not appreciated that parasites of humans (parasitic protozoa and parasitic helminths) represent our most common and even ubiquitous pathogens. Parasites are important causes of human pathology and disease that rival our great killer infections, such as tuberculosis, HIV/AIDS, diarrheal diseases, and lower respiratory infections. Shown in Table 46­1 is the most recent assessment of the global public health impact of human parasitic diseases, as determined by the Global Burden of Disease Study 2016 (GBD 2016 Causes of Death Collaborators, 2017; GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017). TABLE 46­1 Ranking of Human Parasitic Diseases Either by Deaths or Numbers of Prevalent or Incident Cases, Based on the Global Burden of Disease Study 2016 Rank Disease Numbers of Deaths (GBD 2016 Causes of Death Collaborators, 2017) 1 Malaria 719,600 2 Visceral 13,700 leishmaniasis 3 Schistosomiasis 10,100 4 Chagas disease 7,100 5 Ascariasis 4,900 Total for the 755,400 five leading causes Rank Disease Numbers of Prevalent or Incident Cases (GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017) and DALYs (disability­adjusted life years measures overall disease burden, expressed as the number of years lost due to ill­health, disability or early death) (GBD 2016 DALYs and HALE Collaborators, 2017) 1 Ascariasis 800 million prevalent cases (1.3 million DALYs) 2 Hookworm 451 million prevalent cases (1.7 million DALYs) 3 Trichuriasis 435 million prevalent cases (0.3 million DALYs) 4 Malaria 213 million incident cases (56.2 million DALYs) 5 Schistosomiasis 190 million prevalent cases (1.9 million DALYs) Downloaded 2024­8­3 Total for 12:48 the A >2 Your IP prevalent billion is 110.170.245.233 or incident cases (61.4 million DALYs) Chapter 46: Medical Parasitology, five leading Page 1 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility causes pathogens. Parasites are important causes of human pathology and disease that rival our great killer infections, such as tuberculosis, HIV/AIDS, Access Provided by: diarrheal diseases, and lower respiratory infections. Shown in Table 46­1 is the most recent assessment of the global public health impact of human parasitic diseases, as determined by the Global Burden of Disease Study 2016 (GBD 2016 Causes of Death Collaborators, 2017; GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017). TABLE 46­1 Ranking of Human Parasitic Diseases Either by Deaths or Numbers of Prevalent or Incident Cases, Based on the Global Burden of Disease Study 2016 Rank Disease Numbers of Deaths (GBD 2016 Causes of Death Collaborators, 2017) 1 Malaria 719,600 2 Visceral 13,700 leishmaniasis 3 Schistosomiasis 10,100 4 Chagas disease 7,100 5 Ascariasis 4,900 Total for the 755,400 five leading causes Rank Disease Numbers of Prevalent or Incident Cases (GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017) and DALYs (disability­adjusted life years measures overall disease burden, expressed as the number of years lost due to ill­health, disability or early death) (GBD 2016 DALYs and HALE Collaborators, 2017) 1 Ascariasis 800 million prevalent cases (1.3 million DALYs) 2 Hookworm 451 million prevalent cases (1.7 million DALYs) 3 Trichuriasis 435 million prevalent cases (0.3 million DALYs) 4 Malaria 213 million incident cases (56.2 million DALYs) 5 Schistosomiasis 190 million prevalent cases (1.9 million DALYs) Total for the >2 billion prevalent or incident cases (61.4 million DALYs) five leading causes Together, the five leading causes of parasitic deaths resulted in over 750,000 deaths in 2016, with most of those deaths caused by malaria (GBD 2016 Causes of Death Collaborators, 2017). To put that number in perspective, the only specific infectious diseases that outrank malaria or parasitic diseases overall are tuberculosis (1.213 million deaths) and HIV/AIDS (1.033 million deaths) (GBD 2016 Causes of Death Collaborators, 2017). However, even these estimates for parasitic infections may not fully consider all of the deaths, given that many of the deaths from kidney and liver disease resulting from schistosomiasis, or anemia from hookworm, are frequently attributed to other causes, and there are suggestions that the numbers of people dying from sudden death or heart failure from Chagas disease annually may be much higher than previously realized (Herricks et al, 2017). Another striking feature of parasitic diseases is the observation that they occur universally among people who live in poverty. The entire population of the world’s poor is affected either by malaria or by helminth infections, led by the three soil­transmitted helminth infections and schistosomiasis (GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017). Together these parasitic infections cause more than 60 million DALYs (disability­adjusted life years), which exceed the disability of either tuberculosis or HIV/AIDS (GBD 2016 DALYs and HALE Collaborators, 2017). Beyond Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 the disability Chapter and deaths 46: Medical from parasitic diseases is their impact on the global economy. It has been noted that parasitic diseases prevent people Parasitology, Page from 2 / 54 ©2024 escapingMcGraw povertyHill. dueAll Rights to their Reserved. effects Terms on human of Use work productive Privacy Policyand capacity Notice Accessibility child development (Hotez et al, 2009). We are still in the early stages of examining the financial impact of parasites, but the evidence so far indicates that it is substantial and a major reason for inter­generational poverty. This finding is especially relevant given recent evidence that parasitic diseases are also widespread among the poor living in wealthier nations, people dying from sudden death or heart failure from Chagas disease annually may be much higher than previously realized (Herricks et al, 2017). Access Provided by: Another striking feature of parasitic diseases is the observation that they occur universally among people who live in poverty. The entire population of the world’s poor is affected either by malaria or by helminth infections, led by the three soil­transmitted helminth infections and schistosomiasis (GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017). Together these parasitic infections cause more than 60 million DALYs (disability­adjusted life years), which exceed the disability of either tuberculosis or HIV/AIDS (GBD 2016 DALYs and HALE Collaborators, 2017). Beyond the disability and deaths from parasitic diseases is their impact on the global economy. It has been noted that parasitic diseases prevent people from escaping poverty due to their effects on human productive work capacity and child development (Hotez et al, 2009). We are still in the early stages of examining the financial impact of parasites, but the evidence so far indicates that it is substantial and a major reason for inter­generational poverty. This finding is especially relevant given recent evidence that parasitic diseases are also widespread among the poor living in wealthier nations, including the United States, European countries, and Australia, where they are significant health disparities (Hotez, 2016). This chapter offers a brief survey of the protozoan and helminthic parasites of medical importance. A synopsis of each parasite is provided within tables that are organized by the organ system that is infected (eg, intestinal and blood/tissue protozoan infections and intestinal and blood/tissue helminthic infections). Key concepts are provided at the beginning of the protozoa and helminths sections to give the reader an overview of the paradigms in medical parasitology. Current updates to information provided in this chapter can be found at the Centers for Disease Control and Prevention (CDC) website www.cdc.gov/ncidod/dpd. CLASSIFICATION OF PARASITES The parasites covered in this chapter are categorized into two major groups: parasitic protozoa and parasitic helminths. Protozoa are unicellular eukaryotes that form an entire kingdom. Classifying protozoan parasites into taxonomic groups is an ongoing process, and their status is often in a state of flux. For this reason, this chapter separates the parasitic protozoa into four traditional groups based on their means of locomotion and mode of reproduction: flagellates, amebae, sporozoa, and ciliates. Table 46­2 lists several medically important protozoan parasites by the organ system they infect, the mode of infection, diagnosis, treatment, and geographic location. TABLE 46­2 Synopsis of Protozoan Infections by Organ System Site of Geographic Parasite/Disease Mechanism of Infection Diagnosis Treatment Infection Area Intestinal protozoa G. lamblia Small intestine Ingest cysts in water, not killed Stool exam for O&P; Metronidazole or Ubiquitous: (flagellate) by normal chlorination EIA; DFA assay nitazoxanide campers, ski Giardiasis resorts, dogs, wild animals, especially beavers E. histolytica Colon; liver; Ingest cysts from fecal Stool exam for O&P; Iodoquinol, or Worldwide (ameba) other organs contamination of water or EIA for antibodies and paromomycin; wherever fecal Amebiasis food or oral/anal behaviors antigen metronidazole for mild, contamination moderate, severe intestinal occurs disease Cryptosporidium Small intestine; Ingest oocysts, fecal Stool exam/modified Nitazoxanide for Ubiquitous, (sporozoa) respiratory tract contamination acid­fast staining; EIA; immunocompetent especially in Cryptosporidiosis DFA assay cattle­raising areas Cyclospora Small intestine Oocysts from fecal Stool exam/modified Trimethoprim– Worldwide, (sporozoa) contamination of water, fresh acid­fast staining, UV sulfamethoxazole tropics, Cyclosporiasis produce fluorescence subtropics Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 microscopy Chapter 46: Medical Parasitology, Page 3 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Sexually transmitted protozoa  Cryptosporidiosis DFA assay cattle­raising Access Provided by: areas Cyclospora Small intestine Oocysts from fecal Stool exam/modified Trimethoprim– Worldwide, (sporozoa) contamination of water, fresh acid­fast staining, UV sulfamethoxazole tropics, Cyclosporiasis produce fluorescence subtropics microscopy Sexually transmitted protozoa T. vaginalis Vagina; males Trophozoites passed from Microscopic exam of Metronidazole for both Ubiquitous in (flagellate) usually person to person through discharge, urine, tissue partners sexually active Trichomoniasis asymptomatic sexual intercourse scraping populations Blood and tissue flagellates T. brucei Blood, lymph Tsetse bite (painful) lacerates Trypomastigotes Hemolytic stage: Suramin East Africa; rhodesiense skin and releases (extracellular) in CNS involvement: antelope, East African trypomastigotes blood smear, CSF, or Melarsoprol bushbuck are trypanosomiasis, lymph node aspirate; animal reservoirs sleeping sickness serology (CATT) for human infection T. brucei gambiense Blood, lymph Tsetse bite (painful) lacerates Trypomastigotes Hemolytic stage: West Africa; West African skin and releases (extracellular) in pentamidine vegetation trypanosomiasis, trypomastigotes blood smear, CSF, or CNS involvement: around rivers; sleeping sickness lymph node aspirate; Eflornithine humans only serology (CATT) (not zoonotic) Trypanosoma cruzi Amastigotes Kissing bug feces rubbed into Trypomastigotes Benznidazole North, Central, Chagas disease intracellular; bite or eye; blood transfusion; (extracellular) in and South heart, transplacental transmission blood smear; PCR; America (bugs parasympathetic intracellular live in thatched ganglia amastigotes in tissue roofs, mud bx; serology cracks) Leishmania major Skin; rolled edge Sand fly injects promastigotes; Skin bx at edge of Stibogluconate sodium, Mid­East, India, Leishmania tropica ulceration amastigotes in macrophages, ulcer; histopathology; meglumine antimonate, North Africa cutaneous monocytes culture and PCR of miltefosine leishmaniasis organisms Leishmania Skin; rolled edge Sand fly injects promastigotes; Skin bx at edge of Stibogluconate sodium, Mexico, Central & mexicana complex ulceration amastigotes in macrophages, ulcer; histopathology; meglumine antimonate, South America; cutaneous monocytes culture and PCR of miltefosine chiclero ulcers on leishmaniasis organisms ears of chicle harvesters in Yucatan Leishmania Skin; anergy Sand fly injects promastigotes; Skin bx at edge of Sodium stibogluconate, Ethiopia, aethiopica, resulting in amastigotes in macrophages, ulcer; histopathology; meglumine, antimonate, Venezuela Leishmania nonulcerating monocytes culture and PCR of miltefosine mexicana pifanoi lesions over organisms Disseminated or entire body diffuse form of cutaneous leishmaniasis Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Leishmania Skin lesion; may Sand fly injects promastigotes; Skin bx of mucosal Sodium stibogluconate, Brazil, Peru,Page 4 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility braziliensis complex destroy amastigotes in macrophages, tissue; meglumine antimonite, Bolivia Mucocutaneous mucocutaneous monocytes histopathology; miltefosine  Leishmania nonulcerating monocytes culture and PCR of miltefosine Access Provided by: mexicana pifanoi lesions over organisms Disseminated or entire body diffuse form of cutaneous leishmaniasis Leishmania Skin lesion; may Sand fly injects promastigotes; Skin bx of mucosal Sodium stibogluconate, Brazil, Peru, braziliensis complex destroy amastigotes in macrophages, tissue; meglumine antimonite, Bolivia Mucocutaneous mucocutaneous monocytes histopathology; miltefosine leishmaniasis tissues on face, culture and PCR of mouth organisms Leishmania Sand fly injects promastigotes; Bx spleen, liver, bone Liposomal amphotericin B, Post­kala­azar donovani amastigotes in macrophages marrow aspirate; sodium stibogluconate, dermal Kala­azar, visceral and monocytes of spleen, histopathology; meglumine antimonite, leishmaniasis 1–3 leishmaniasis liver, bone marrow culture and PCR of miltefosine years after Rx organisms; serology India, Sudan, South Sudan, Ethiopia, Kenya, Brazil Tissue amebae Naegleria, Brain, spinal Swimming in warm freshwater Trophozoite in CSF; Amphotericin B; Where free­living Acanthamoeba, cord, eye lakes, ponds, rivers, hot microscopic exam of miltefosine; CDC amebae survive Balamuthia springs; free­living amebae tissue bx; clinical Emergency Operations in sediment of Primary amebic enter nasal membrane, pass suspicion based on Center 770­488­7100 warm waters meningoencephalitis to brain or via wound or recent history of (Entamoeba penetration of eye swimming or diving in histolytica— (Acanthamoeba) warm waters amebiasis, see intestinal protozoa) Blood and tissue sporozoa Plasmodium vivax Intracellular in Female Anopheles mosquito Thick and thin blood aUncomplicated vivax: Asia, Central & malaria RBCs; releases sporozoites into smears; ring stage in chloroquine plus South America, hypnozoites in bloodstream; parasites enter RBCs with Schüffner primaquine (where no some areas of liver can cause liver, then blood; can relapse dots; RDTs resistance), otherwise Africa (rare in relapse quinine plus doxycycline or west Africa) tetracycline plus primaquine for relapse Plasmodium Intracellular in Female Anopheles mosquito Thick and thin blood aUncomplicated Worldwide in falciparum RBCs releases sporozoites into smears; banana­ falciparum: chloroquine tropical and Malaria bloodstream; parasites enter shaped gametocytes; (where no resistance), subtropical areas liver, then blood; no relapse double rings in RBCs; otherwise RDTs artemether/lumefantrine (Coartem, artemisinin­ based combination therapy, ACT) Plasmodium ovale Intracellular in Female Anopheles mosquito Thick and thin blood aUncomplicated malaria: Sub­Saharan Malaria RBCs; releases sporozoites into smears chloroquine (where no Africa, especially hypnozoites in bloodstream; parasites enter resistance); primaquine for West Africa; Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 liver can cause Chapter 46: Medical Parasitology, liver, then blood; can relapse relapse Islands of Page 5 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility relapse western Pacific Plasmodium Intracellular in Enters liver from inoculation Thick and thin blood Chloroquine (where no Worldwide  based combination Access Provided by: therapy, ACT) Plasmodium ovale Intracellular in Female Anopheles mosquito Thick and thin blood aUncomplicated malaria: Sub­Saharan Malaria RBCs; releases sporozoites into smears chloroquine (where no Africa, especially hypnozoites in bloodstream; parasites enter resistance); primaquine for West Africa; liver can cause liver, then blood; can relapse relapse Islands of relapse western Pacific Plasmodium Intracellular in Enters liver from inoculation Thick and thin blood Chloroquine (where no Worldwide malariae RBCs; into bloodstream by infected smears resistance) Malaria hypnozoites in mosquito; no relapse liver can cause relapse Plasmodium Intracellular in Female Anopheles mosquito Thick and thin blood Chloroquine (where no Southeast Asia knowlesi RBCs releases sporozoites into smears resistance) Primate malaria bloodstream; parasites enter liver, then blood; hypnozoites not yet found Babesia microti Intracellular in Tick bite; blood transfusions Thick and thin blood Atovaquone plus USA, Europe Babesiosis RBCs smears; tetrad forms azithromycin; clindamycin (“Maltese Cross”) plus quinine inside RBCs Toxoplasma gondii Intracellular in Ingestion of parasites in Serology (IgG and IgM) Pyrimethamine plus Worldwide; areas Toxoplasmosis CNS, bone undercooked meat; ingestion sulfadiazine where cats/felids marrow of oocysts from cat feces; live transplacental; blood transfusion Abbreviations: CATT, card agglutination test for trypanosomes; CNS, central nervous system; CSF, cerebrospinal fluid; DFA, direct immunofluorescence assay; EIA, enzyme immunoassay; IFA, indirect fluorescent assay; O&P, ova and parasites; PCR, polymerase chain reaction; RBC, red blood cell; RDTs, rapid diagnostic tests. aRecommendations should be checked regularly (www.cdc.gov/malaria/diagnosis_treatment/index.html) and CDC Malaria Hotline: (770) 488­7788 or (855) 856­4713 toll­free Monday­Friday 9 am to 5 pm EST ­ (770) 488­7100 after hours, weekends and holidays. Starting on April 1, 2019, clinicians treating patients with severe malaria should call CDC to obtain IV artesunate (https://www.cdc.gov/malaria/new_info/2019/artesunate_2019.html). For a review of malaria treatment, see Rosenthal PJ, 2015. (1) Flagellates have one or more whip­like flagella and, in some cases, an undulating membrane (eg, trypanosomes). These include intestinal and genitourinary flagellates (Giardia and Trichomonas, respectively) and blood and tissue flagellates (Trypanosoma and Leishmania). (2) Amebae are typically ameboid and use pseudopodia or protoplasmic flow to move. They are represented in humans by species of Entamoeba, Naegleria, and Acanthamoeba. (3) Sporozoa undergo a complex life cycle with alternating sexual and asexual reproductive phases. The human parasites, such as Cryptosporidium, Cyclospora, and Toxoplasma, and the malarial parasites (Plasmodium species) are all intracellular parasites. (4) Ciliates are complex protozoa bearing cilia distributed in rows or patches, with two kinds of nuclei in each individual. Balantidium coli, a giant intestinal ciliate of humans and pigs, is the only human parasite representative of this group, and because the disease is considered rare, it is not covered in this chapter. Formerly listed with the sporozoa, because they possess polar filaments within a spore, microsporidia include more than 1000 species of intracellular parasites that infect invertebrates (mostly insects) and vertebrate hosts. In humans, microsporidians are opportunistic parasites of immunocompromised patients, including those undergoing chemotherapy and organ transplants. Pneumocystis jiroveci was long considered a protozoan parasite but has been shown to be a member of the fungi rather than the protozoa. It causes interstitial plasma cell pneumonitis in immunosuppressed individuals and is considered an opportunistic pathogen. The majority of parasitic helminths that infect humans belong to two phyla: Nematoda (roundworms) and Platyhelminthes (flatworms). Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 6 / 54 (1) Nematodes are among the most speciose and diverse animals. They are elongated and tapered at both ends, round in cross­section, and ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility unsegmented. They have only a set of longitudinal muscles, which allows them to move in a whip­like, penetrating fashion; a complete digestive system that is well adapted for ingestion of the host’s gut contents, cells, blood, or cellular breakdown products; and a highly developed separate­sexed intracellular parasites that infect invertebrates (mostly insects) and vertebrate hosts. In humans, microsporidians are opportunistic parasites of immunocompromised patients, including those undergoing chemotherapy and organ transplants. Access Provided by: Pneumocystis jiroveci was long considered a protozoan parasite but has been shown to be a member of the fungi rather than the protozoa. It causes interstitial plasma cell pneumonitis in immunosuppressed individuals and is considered an opportunistic pathogen. The majority of parasitic helminths that infect humans belong to two phyla: Nematoda (roundworms) and Platyhelminthes (flatworms). (1) Nematodes are among the most speciose and diverse animals. They are elongated and tapered at both ends, round in cross­section, and unsegmented. They have only a set of longitudinal muscles, which allows them to move in a whip­like, penetrating fashion; a complete digestive system that is well adapted for ingestion of the host’s gut contents, cells, blood, or cellular breakdown products; and a highly developed separate­sexed reproductive system. They shed their tough cuticles (molt) as they undergo development from larvae to adults, and the eggs and larval stages are well suited for survival in the external environment. Most human infections are acquired by ingestion of the egg or larval stage, but nematode infections can also be acquired from insect vectors and skin penetration. (2) Platyhelminths are flatworms that are dorsoventrally flattened in cross­section and are hermaphroditic, with a few exceptions. All medically important species belong to two classes: Trematoda (flukes) and Cestoda (tapeworms). Trematodes are typically flattened and leaf shaped with two muscular suckers. They have a bifurcated gut and possess both circular and longitudinal muscles; they lack the cuticle characteristic of nematodes and instead have a syncytial epithelium. Trematodes are hermaphroditic, with the exception of the schistosomes (blood flukes), which have male and female worms that exist coupled together within small blood vessels of their hosts. The life cycle of human trematodes is typically initiated when eggs are passed into fresh water via feces or urine. Eggs develop, hatch, and release a ciliated miracidium, which infects a snail host that is usually highly specific to the fluke species. Within the snail, the miracidium develops into a sporocyst, which contains germinal cells that ultimately develop into the final larval stage—the cercariae. These swim out of the snail and encyst as metacercariae in a second intermediate host or on vegetation, depending on the species. Most fluke infections are acquired by ingestion of the metacercariae. The cercariae of schistosomes, however, directly penetrate the skin of their hosts and do not encyst as metacercariae. Cestodes, or tapeworms, are flat and have a ribbon­like chain of segments (proglottids) containing male and female reproductive structures. Adult tapeworms can reach lengths of 10 m and have hundreds of segments, with each segment releasing thousands of eggs. At the anterior end of an adult tapeworm is the scolex, which is often elaborated with muscular suckers, hooks, or structures that aid in its ability to attach to the intestinal wall. Adult tapeworms have no mouth or gut and absorb their nutrients directly from their host through their integument. The life cycle of cestodes, like that of the trematodes, is usually indirect (involving one or more intermediate hosts and a final host). Eggs are excreted with the feces and ingested by an intermediate host (invertebrate, such as a flea, or vertebrate, such as a mammal); the larvae develop into certain forms that are peculiar to the specific species within the intermediate host (eg, cysticercus in the case of Taenia solium or hydatid cyst with Echinococcus granulosus). Cestode larvae are generally eaten, and the larva develops into an adult worm in the intestine of the final host. INTESTINAL PROTOZOAN INFECTIONS A synopsis of the parasitic protozoan infections is provided in Table 46­2. Key concepts pertaining to parasitic protozoa and a list of the protozoa in this chapter are included in Tables 46­3 and 46­4. TABLE 46­3 Key Concepts: Parasitic Protozoa Parasitic protozoa covered in this chapter are grouped into the flagellates, amebae, sporozoa, and ciliates. Flagellates and amebae multiply by binary fission; sporozoans reproduce by a process known as merogony (also called schizogony) in which the nuclei replicate prior to cytokinesis. Sporozoans (Cryptosporidium, Plasmodium, Toxoplasma) undergo sexual recombination, which leads to genomic and antigenic variation. Protozoa can multiply quickly (on the order of several hours) in the host and can cause a rapid onset of symptoms. Intestinal infections are acquired by ingestion of an environmentally resistant cyst (or oocyst) form; blood infections are vectorborne. Infections by intracellular protozoa (Trypanosoma cruzi, Leishmania spp., Cryptosporidium, Toxoplasma, and Plasmodium) are difficult to treat because drugs must cross plasma membranes. No vaccines are available for any human parasitic disease. Downloaded 2024­8­3 Latent infections 12:48 occur withAToxoplasma Your IP is(parasites 110.170.245.233 in tissue cysts are called bradyzoites) and Plasmodium vivax and Plasmodium ovale (parasites in liver Chapter 46: Medical Parasitology, tissue are called hypnozoites). Page 7 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility In disseminated protozoal infections, fever and flulike symptoms occur and are nonspecific. INTESTINAL PROTOZOAN INFECTIONS Access Provided by: A synopsis of the parasitic protozoan infections is provided in Table 46­2. Key concepts pertaining to parasitic protozoa and a list of the protozoa in this chapter are included in Tables 46­3 and 46­4. TABLE 46­3 Key Concepts: Parasitic Protozoa Parasitic protozoa covered in this chapter are grouped into the flagellates, amebae, sporozoa, and ciliates. Flagellates and amebae multiply by binary fission; sporozoans reproduce by a process known as merogony (also called schizogony) in which the nuclei replicate prior to cytokinesis. Sporozoans (Cryptosporidium, Plasmodium, Toxoplasma) undergo sexual recombination, which leads to genomic and antigenic variation. Protozoa can multiply quickly (on the order of several hours) in the host and can cause a rapid onset of symptoms. Intestinal infections are acquired by ingestion of an environmentally resistant cyst (or oocyst) form; blood infections are vectorborne. Infections by intracellular protozoa (Trypanosoma cruzi, Leishmania spp., Cryptosporidium, Toxoplasma, and Plasmodium) are difficult to treat because drugs must cross plasma membranes. No vaccines are available for any human parasitic disease. Latent infections occur with Toxoplasma (parasites in tissue cysts are called bradyzoites) and Plasmodium vivax and Plasmodium ovale (parasites in liver tissue are called hypnozoites). In disseminated protozoal infections, fever and flulike symptoms occur and are nonspecific. Some parasitic protozoa are able to evade the host’s immune response because they are intracellular and/or undergo antigenic variation. TABLE 46­4 Parasitic Protozoa Intestinal protozoa G. lamblia (flagellate) Entamoeba histolytica (ameba) Cryptosporidium hominis (sporozoa) Cyclospora cayetanensis (sporozoa) Sexually transmitted protozoan infection Trichomonas vaginalis (flagellate) Blood and tissue protozoan infections Flagellates T. brucei rhodesiense and T. brucei gambiense T. cruzi Leishmania donovani, Leishmania tropica, Leishmania mexicana Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter Amebae 46: Medical Parasitology, Page 8 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Entamoeba histolytica (see intestinal protozoa)  In disseminated protozoal infections, fever and flulike symptoms occur and are nonspecific. Access Provided by: Some parasitic protozoa are able to evade the host’s immune response because they are intracellular and/or undergo antigenic variation. TABLE 46­4 Parasitic Protozoa Intestinal protozoa G. lamblia (flagellate) Entamoeba histolytica (ameba) Cryptosporidium hominis (sporozoa) Cyclospora cayetanensis (sporozoa) Sexually transmitted protozoan infection Trichomonas vaginalis (flagellate) Blood and tissue protozoan infections Flagellates T. brucei rhodesiense and T. brucei gambiense T. cruzi Leishmania donovani, Leishmania tropica, Leishmania mexicana Amebae Entamoeba histolytica (see intestinal protozoa) Naegleria fowleri and Acanthamoeba castellanii Sporozoa Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, and Plasmodium malariae Babesia microti Toxoplasma gondii Microsporidia GIARDIA LAMBLIA (INTESTINAL FLAGELLATE) The Organism G. lamblia (also referred to as Giardia duodenalis or Giardia intestinalis) is the causative agent of giardiasis and is the only common pathogenic protozoan found in the duodenum and jejunum of humans. Giardia exists in two forms: the trophozoite and the cyst forms. The trophozoite of G. lamblia is a heart­shaped organism, has four pairs of flagella, and is approximately 15 μm in length (Figure 46­1A). A large concave sucking disk on the ventral surface2024­8­3 Downloaded helps the12:48 organism A Yourto adhere to intestinal villi. As the parasites pass into the colon, they typically encyst, and the cysts are passed in the IP is 110.170.245.233 Chapter 46: Medical stool (Figure Parasitology, 46­1B). They are ellipsoid, thick­walled, highly resistant, and 8–14 μm in length; they contain two nuclei as immature forms and Page four9as/ 54 ©2024 McGraw mature cysts. Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility FIGURE 46­1 The Organism Access Provided by: G. lamblia (also referred to as Giardia duodenalis or Giardia intestinalis) is the causative agent of giardiasis and is the only common pathogenic protozoan found in the duodenum and jejunum of humans. Giardia exists in two forms: the trophozoite and the cyst forms. The trophozoite of G. lamblia is a heart­shaped organism, has four pairs of flagella, and is approximately 15 μm in length (Figure 46­1A). A large concave sucking disk on the ventral surface helps the organism to adhere to intestinal villi. As the parasites pass into the colon, they typically encyst, and the cysts are passed in the stool (Figure 46­1B). They are ellipsoid, thick­walled, highly resistant, and 8–14 μm in length; they contain two nuclei as immature forms and four as mature cysts. FIGURE 46­1 Giardia lamblia. A : Trophozoite (12–15 μm). (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) B : Cyst (11–14 μm). (Courtesy of D. Petrovic, Microbiology Section, Clinical Laboratories, UCSF.) Pathology and Pathogenesis G. lamblia is usually only weakly pathogenic for humans. Cysts may be found in large numbers in the stools of entirely asymptomatic persons. In some persons, however, large numbers of parasites attached to the bowel wall may cause irritation and low­grade inflammation of the duodenal or jejunal mucosa, with consequent acute or chronic diarrhea associated with crypt hypertrophy, villous atrophy or flattening, and epithelial cell damage. Stools may be watery, semisolid, greasy, bulky, and foul smelling at various times during the course of the infection. Symptoms of malaise, weakness, weight loss, abdominal Downloaded cramps,12:48 2024­8­3 distention, A Your and IPflatulence may continue for long periods. Collecting multiple stool samples over several days is recommended is 110.170.245.233 Chapter 46:the to increase Medical Parasitology, likelihood of microscopically detecting cysts in smears. Page 10 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Epidemiology  Access Provided by: G. lamblia is usually only weakly pathogenic for humans. Cysts may be found in large numbers in the stools of entirely asymptomatic persons. In some persons, however, large numbers of parasites attached to the bowel wall may cause irritation and low­grade inflammation of the duodenal or jejunal mucosa, with consequent acute or chronic diarrhea associated with crypt hypertrophy, villous atrophy or flattening, and epithelial cell damage. Stools may be watery, semisolid, greasy, bulky, and foul smelling at various times during the course of the infection. Symptoms of malaise, weakness, weight loss, abdominal cramps, distention, and flatulence may continue for long periods. Collecting multiple stool samples over several days is recommended to increase the likelihood of microscopically detecting cysts in smears. Epidemiology G. lamblia occurs worldwide. Humans are infected by ingestion of fecally contaminated water or food containing Giardia cysts or by direct fecal contamination, as may occur in day­care centers, refugee camps, and institutions, or during oral–anal sex. Epidemic outbreaks have been reported at ski resorts in the United States, where overloading of sewage facilities or contamination of the water supply has resulted in sudden outbreaks of giardiasis. Cysts can survive in water for up to 3 months. Outbreaks among campers in wilderness areas suggest that humans may be infected with various animal giardia harbored by rodents, deer, cattle, sheep, horses, or household pets. ENTAMOEBA HISTOLYTICA (INTESTINAL AND TISSUE AMEBA) The Organism E. histolytica cysts are present only in the lumen of the colon and in mushy or formed feces and range in size from 10 to 20 μm (Figure 46­2A). The cyst may contain a glycogen vacuole and chromatoid bodies (masses of ribonucleoprotein) with characteristic rounded ends (in contrast to splinter chromatoidals in developing cysts of Entamoeba coli). Nuclear division occurs within the cyst, resulting in a quadrinucleated cyst, and the chromatoid bodies and glycogen vacuoles disappear. Diagnosis in most cases rests on the characteristics of the cyst, as trophozoites usually appear only in diarrheic feces in active cases and survive for only a few hours. FIGURE 46­2 Entamoeba histolytica. A : Cyst (12–15 μm) with two (of four) nuclei and a chromatoid body. B : Trophozoite (10–20 μm). (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 11 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility  Access Provided by: The ameboid trophozoite is the only form present in tissues (Figure 46­2B). The cytoplasm has two zones, a hyaline outer margin and a granular inner region that may contain red blood cells (pathognomonic) but ordinarily contains no bacteria. The nuclear membrane is lined by fine, regular granules of chromatin with a small central body (endosome or karyosome). Pathology and Pathogenesis of Invasive Amebiasis It is estimated that approximately 50 million cases occur each year, with up to 100,000 deaths (Marie and Petri, 2014). Disease results when the trophozoites of E. histolytica invade the intestinal epithelium and form discrete ulcers with a pinhead­sized center and raised edges, from which mucus, necrotic cells, and amebae pass. The trophozoites multiply and accumulate above the muscularis mucosae, often spreading laterally. Rapid lateral spread of the multiplying amebae follows, undermining the mucosa and producing the characteristic “flask­shaped” ulcer of primary amebiasis: a small point of entry, leading via a narrow neck through the mucosa into an expanded necrotic area in the submucosa. Bacterial invasion usually does not occur at this time, cellular reaction is limited, and damage is by lytic necrosis. Subsequent spread may coalesce colonies of amebae, undermining large areas of the mucosal surface. Trophozoites may penetrate the muscle layers and occasionally the serosa, leading to perforation into the peritoneal cavity. Subsequent enlargement of the necrotic area produces gross changes in the ulcer, which may develop shaggy overhanging edges, secondary bacterial invasion, and accumulation of neutrophilic leukocytes. Secondary intestinal lesions may develop as extensions from the primary lesion (usually in the cecum, appendix, or nearby portion of the ascending colon). The organisms may travel to the ileocecal valve and terminal ileum, producing a chronic infection. The sigmoid colon and rectum are favored sites for later lesions. An amebic inflammatory or granulomatous tumorlike mass (ameboma) may form on the intestinal wall, sometimes growing sufficiently large to block the lumen. Factors that determine invasion of amebae include the following: the number of amebae ingested, the pathogenic capacity of the parasite strain, host factors such as gut motility and immune competence, and the presence of suitable enteric bacteria that enhance amebic growth. Correct and prompt identification of the Entamoeba species remains a critical problem. Trophozoites, especially with red blood cells in the cytoplasm, found in liquid or semi­formed stools are pathognomonic. Symptoms vary greatly depending on the site and intensity of lesions. Extreme abdominal tenderness, fulminating dysentery, dehydration, and incapacitation occur in serious disease. In less acute disease, onset of symptoms is usually gradual and often includes episodes of diarrhea, abdominal cramps, nausea and vomiting, and an urgent desire to defecate. More frequently, there will be weeks of cramps and general discomfort, loss of appetite, and weight loss, with general malaise. Symptoms may develop within 4 days of exposure, may occur up to a year later, or may never occur. Downloaded Extraintestinal2024­8­3 infection12:48 A Yourand is metastatic IP is 110.170.245.233 rarely occurs by direct extension from the bowel. By far the most common form is amebic hepatitis or liver Chapter 46: Medical Parasitology, Page 12 / 54 abscess (4% or more of clinical infections), which is assumed to be due to microemboli, including trophozoites carried through the portal circulation. It ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility is assumed that hepatic microembolism with trophozoites is a common accompaniment of bowel lesions but that these diffuse focal lesions rarely progress. A true amebic abscess is progressive, nonsuppurative (unless secondarily infected), and destructive without compression and formation of a  Access Provided by: Symptoms vary greatly depending on the site and intensity of lesions. Extreme abdominal tenderness, fulminating dysentery, dehydration, and incapacitation occur in serious disease. In less acute disease, onset of symptoms is usually gradual and often includes episodes of diarrhea, abdominal cramps, nausea and vomiting, and an urgent desire to defecate. More frequently, there will be weeks of cramps and general discomfort, loss of appetite, and weight loss, with general malaise. Symptoms may develop within 4 days of exposure, may occur up to a year later, or may never occur. Extraintestinal infection is metastatic and rarely occurs by direct extension from the bowel. By far the most common form is amebic hepatitis or liver abscess (4% or more of clinical infections), which is assumed to be due to microemboli, including trophozoites carried through the portal circulation. It is assumed that hepatic microembolism with trophozoites is a common accompaniment of bowel lesions but that these diffuse focal lesions rarely progress. A true amebic abscess is progressive, nonsuppurative (unless secondarily infected), and destructive without compression and formation of a wall. The contents are necrotic and bacteriologically sterile, active amebae being confined to the walls. A characteristic “anchovy paste” is produced in the abscess and seen on surgical drainage. More than half of patients with amebic liver abscess give no history of intestinal infection, and rarely, amebic abscesses occur elsewhere (eg, lung, brain, and spleen). Any organ or tissue in contact with active trophozoites may become a site of invasion and abscess. Hepatic abscess, usually showing as an elevation of the right dome of the diaphragm, can be observed by ultrasonography, computerized tomography, magnetic resonance imaging, or radioisotope scanning. Serologic tests in these cases are usually strongly positive. OTHER INTESTINAL AMEBAE Invasive or pathogenic E. histolytica is now considered a species distinct from the more common lumen­dwelling nonpathogenic commensal species, Entamoeba dispar, with the name E. histolytica reserved only for the pathogenic form. E. dispar and the related Entamoeba moshkovskii are, based on isoenzyme, genetic, and PCR analyses, distinct species, even though they are microscopically identical. E. histolytica must be distinguished not only from E. dispar and E. moshkovskii but also from four other ameba­like organisms that are also intestinal parasites of humans: (1) E. coli, which is very common; (2) Dientamoeba fragilis (a flagellate), the only intestinal parasite other than E. histolytica that has been suspected of causing diarrhea and dyspepsia but is not invasive; (3) Iodamoeba bütschlii; and (4) Endolimax nana. Considerable experience is required to distinguish E. histolytica from other forms, but it is necessary to do so because misdiagnosis often leads to unnecessary treatment, overtreatment, or failure to treat. Enzyme immunoassay (EIA) kits are available commercially for serodiagnosis of amebiasis when stools are often negative. EIA tests to detect amebic antigen in the stool are also sensitive and specific for E. histolytica and can distinguish between pathogenic and nonpathogenic infections (Haque et al, 2003). Epidemiology E. histolytica occurs worldwide, mostly in developing countries where sanitation and hygiene are poor. Infections are transmitted via the fecal–oral route; cysts are usually ingested through contaminated water, vegetables, and food; flies have also been linked to transmission in areas of fecal pollution. Most infections are asymptomatic, with the asymptomatic cyst passers being a source of contamination for outbreaks where sewage leaks into the water supply or breakdown of sanitation occurs (as in mental, geriatric, or children’s institutions or prisons). CRYPTOSPORIDIUM (INTESTINAL SPOROZOA) The Organisms Cryptosporidium species, typically Cryptosporidium hominis, can infect the intestine in immunocompromised persons (eg, those with AIDS) and cause severe, intractable diarrhea. They have long been known as parasites of rodents, fowl, rhesus monkeys, cattle, and other herbivores and have probably been an unrecognized cause of self­limited, mild gastroenteritis and diarrhea in humans. Oocysts measuring 4–5 μm are passed in feces in enormous numbers and are immediately infectious. When oocysts in contaminated foods and water are ingested, sporozoites excyst and invade intestinal cells; the parasites multiply asexually within the apical portion of the intestinal cells, are released, and infect other intestinal cells to begin a new cycle. They also reproduce sexually, forming male microgamonts and female macrogamonts that fuse and develop into oocysts. Pathology and Pathogenesis Cryptosporidium inhabits the brush border of mucosal epithelial cells of the gastrointestinal tract, especially the surface of villi of the lower small bowel (Figure 46­3A). The prominent clinical feature of cryptosporidiosis is watery diarrhea, which is mild and self­limited (1–2 weeks) in normal persons but may be severe and prolonged in immunocompromised or very young or old individuals. The small intestine is the most commonly infected site, but Cryptosporidium infections have also been found in other organs, including other digestive tract organs and the lungs. FIGURE 46­3 Cryptosporidium. A : Histologic section of intestine with organisms (arrows) at the apical portion of the epithelial cells. (Courtesy of Pathology, UCSF.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 B : Oocysts (4–5 μm) stain pink in stool samples stained with a modified acid­fast stain. (Used with permission from Sullivan J: A Color Atlas of Chapter 46: Medical Parasitology, Page 13 / 54 Parasitology ©2024 McGraw , 8thHill. ed. 2009.) All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility persons but may be severe and prolonged in immunocompromised or very young or old individuals. The small intestine is the most commonly infected Access Provided by: site, but Cryptosporidium infections have also been found in other organs, including other digestive tract organs and the lungs. FIGURE 46­3 Cryptosporidium. A : Histologic section of intestine with organisms (arrows) at the apical portion of the epithelial cells. (Courtesy of Pathology, UCSF.) B : Oocysts (4–5 μm) stain pink in stool samples stained with a modified acid­fast stain. (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) Diagnosis depends on detection of oocysts in fresh stool samples. Stool concentration techniques using a modified acid­fast stain are usually necessary (Figure 46­3B), and monoclonal antibody­based tests are available that can detect low levels of fecal antigen. Epidemiology The incubation period for cryptosporidiosis is from 1 to 12 days, and the disease is acquired from infected animal or human feces or from fecally contaminated food or water. For those at high risk (immunocompromised and very young or old persons), avoidance of animal feces and careful attention to sanitation are required. The organisms are widespread and probably infect asymptomatically a significant proportion of the human population. Occasional outbreaks, such as the one that occurred in Milwaukee in early 1993, affecting more than 400,000 people, can result from inadequate protection, treatment, or filtration of water supplies for large urban centers. In that instance, cattle manure from large dairy farms was the source of contamination of the water supply. As few as 30 organisms can initiate an infection—and the ability of the parasite to complete its life cycle, including the sexual phase, within the same individual makes possible the fulminating infections frequently observed in immunosuppressed individuals. Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 CYCLOSPORA (INTESTINAL Chapter 46: Medical Parasitology, SPOROZOA) Page 14 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility The Organism population. Occasional outbreaks, such as the one that occurred in Milwaukee in early 1993, affecting more than 400,000 people, can result from Access Provided by: inadequate protection, treatment, or filtration of water supplies for large urban centers. In that instance, cattle manure from large dairy farms was the source of contamination of the water supply. As few as 30 organisms can initiate an infection—and the ability of the parasite to complete its life cycle, including the sexual phase, within the same individual makes possible the fulminating infections frequently observed in immunosuppressed individuals. CYCLOSPORA (INTESTINAL SPOROZOA) The Organism The life cycle of Cyclospora is similar to that of Cryptosporidium and appears to involve only a single host. Cyclospora, however, differs from Cryptosporidium in that Cyclospora oocysts are not immediately infectious when passed in stools. Unlike Cryptosporidium oocysts, which are infectious in the feces, Cyclospora oocysts take days or weeks to become infectious, and because of this, direct person­to­person transmission through fecal exposure is unlikely to occur. Cyclosporiasis has been linked to waterborne and foodborne infections from various types of fresh produce, including raspberries, mesclun, and basil, since the 1990s (Ortega and Sanchez, 2010). Pathology and Pathogenesis Altered mucosal architecture with shortening of intestinal villi due to diffuse edema and infiltration of inflammatory cells leads to diarrhea, anorexia, fatigue, and weight loss. The duration of symptoms among untreated, nonimmune persons is often prolonged but ultimately self­limited, with remitting­relapsing symptoms lasting up to several weeks or months. The incubation period for Cyclospora infections is about 1 week, similar to infections with Cryptosporidium. Specific requests for laboratory testing of Cyclospora are necessary (same for Cryptosporidium) when examining stools for oocysts (8–10 μm), which are acid­fast positive (reddish). Unlike infections with Cryptosporidium, Cyclospora infections are treatable with trimethoprim–sulfamethoxazole (TMP­SMZ). SEXUALLY TRANSMITTED PROTOZOAN INFECTION TRICHOMONAS VAGINALIS (GENITOURINARY FLAGELLATE) The Organism T. vaginalis exists only as a trophozoite (no cyst stage); it has four free flagella that arise from a single stalk and a fifth flagellum, which forms an undulating membrane. It is pyriform and approximately 20 μm in length and 10 μm wide. Pathology and Pathogenesis T. vaginalis is sexually transmitted, and most infections are asymptomatic or mild for both women and men. In women, the infection is normally limited to the vulva, vagina, and cervix; it does not usually extend to the uterus. The mucosal surfaces may be tender, inflamed, eroded, and covered with a frothy yellow or cream­colored discharge. In men, the prostate, seminal vesicles, and urethra may be infected. Signs and symptoms in females, in addition to profuse vaginal discharge, include local tenderness, vulval pruritus, and burning. About 10% of infected males have a thin, white urethral discharge. The incubation period is from around 5 to 28 days. Epidemiology T. vaginalis is a common parasite of both males and females but infection is more common in women than in men. Infants may be infected during birth. In the United States, it is estimated that 3.7 million people have the infection but only 30% become symptomatic. Control of T. vaginalis infections always requires simultaneous treatment of both sexual partners. Mechanical protection (condoms) should be used during intercourse until the infection is eradicated in both partners. BLOOD AND TISSUE PROTOZOAN INFECTIONS BLOOD FLAGELLATES The hemoflagellates of humans include the genera Trypanosoma and Leishmania (Table 46­5). There are two distinct types of human trypanosomes: (1) African, which causes sleeping sickness and is transmitted by tsetse flies (eg, Glossina): Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and (2) American, which causes Chagas disease and is transmitted by kissing bugs (eg, Triatoma): Trypanosoma cruzi. The genus Leishmania, divided into a number of species infecting humans, causes cutaneous (Oriental sore), mucocutaneous (espundia), and visceral (kala­azar) leishmaniasis. Downloaded All ofAthese 2024­8­3 12:48 Yourinfections are transmitted by sand flies (Phlebotomus in the Old World and Lutzomyia in the New World). IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 15 / 54 TABLE 46­5 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Comparison of the Trypanosoma spp. and Leishmania spp.  Access Provided by: The hemoflagellates of humans include the genera Trypanosoma and Leishmania (Table 46­5). There are two distinct types of human trypanosomes: (1) African, which causes sleeping sickness and is transmitted by tsetse flies (eg, Glossina): Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and (2) American, which causes Chagas disease and is transmitted by kissing bugs (eg, Triatoma): Trypanosoma cruzi. The genus Leishmania, divided into a number of species infecting humans, causes cutaneous (Oriental sore), mucocutaneous (espundia), and visceral (kala­azar) leishmaniasis. All of these infections are transmitted by sand flies (Phlebotomus in the Old World and Lutzomyia in the New World). TABLE 46­5 Comparison of the Trypanosoma spp. and Leishmania spp. Hemoflagellates Disease Vector Stages in Humans Trypanosoma brucei African sleeping sickness (acute) Tsetse fly Trypomastigotes in blood rhodesiense T. brucei gambiense African sleeping sickness (chronic) Tsetse fly Trypomastigotes in blood Trypanosoma cruzi Chagas disease Kissing Trypomastigotes in blood; amastigotes intracellular bug Leishmania spp. Cutaneous, mucocutaneous, visceral Sand fly Amastigotes intracellular in macrophages and leishmaniasis monocytes TRYPANOSOMA BRUCEI RHODESIENSE AND TRYPANOSOMA BRUCEI GAMBIENSE (BLOOD FLAGELLATES) The Organisms Parasites of the genus Trypanosoma appear in the blood as trypomastigotes, with elongated bodies supporting a longitudinal lateral undulating membrane and a flagellum that borders the free edge of the membrane and emerges at the anterior end as a whip­like extension (Figure 46­4). The kinetoplast (circular DNA inside the single mitochondrion) is a darkly staining body lying immediately adjacent to the basal body from which the flagellum arises. T. brucei rhodesiense, T. brucei gambiense, and Trypanosoma brucei brucei (which causes a sleeping sickness called nagana in livestock and game animals) are indistinguishable morphologically but differ biochemically, ecologically, and epidemiologically. FIGURE 46­4 Trypanosoma brucei gambiense (or Trypanosoma brucei rhodesiense, indistinguishable in practice) trypomastigotes (14–35 μm) in a blood smear (red blood cells = 8 μm). (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 16 / 54 ©2024 McGraw Pathology and Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Pathogenesis Infective trypanosomes of T. brucei gambiense and T. brucei rhodesiense are introduced through the bite of the tsetse fly and multiply at the site of FIGURE 46­4 Access Provided by: Trypanosoma brucei gambiense (or Trypanosoma brucei rhodesiense, indistinguishable in practice) trypomastigotes (14–35 μm) in a blood smear (red blood cells = 8 μm). (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) Pathology and Pathogenesis Infective trypanosomes of T. brucei gambiense and T. brucei rhodesiense are introduced through the bite of the tsetse fly and multiply at the site of inoculation to cause variable induration and swelling (the primary lesion), which may progress to form a trypanosomal chancre. The African forms multiply extracellularly as trypomastigotes in the blood as well as in lymphoid tissues. They spread to lymph nodes, to the bloodstream, and, in terminal stages, to the central nervous system (CNS), where they produce the typical sleeping sickness syndrome: lassitude, inability to eat, tissue wasting, unconsciousness, and death. CNS involvement is most characteristic of African trypanosomiasis. T. brucei rhodesiense appears in the cerebrospinal fluid in about 1 month and T. brucei gambiense in several months, but both are present in small numbers. T. brucei gambiense infection is chronic and leads to progressive diffuse meningoencephalitis, with death from the sleeping syndrome usually following in 1–2 years. The more rapidly fatal T. brucei rhodesiense produces somnolence and coma only during the final weeks of a terminal infection. The trypanosomes are transmissible through the placenta, and congenital infections occur in hyperendemic areas. The African trypanosomes of the T. brucei complex are remarkable in that they undergo antigenic variation through a series of genetically controlled surface glycoproteins that coat the surface of the organism (variant surface glycoproteins, or VSGs). Successive waves of parasites in the host bloodstream are each covered with a distinct coat. This process is due to genetically induced changes of the surface glycoprotein. By producing different antigenic surface membranes, the parasite is able to evade the host’s antibody response. Each population is reduced but is promptly replaced with another antigenic type before the preceding one is eliminated. Each trypanosome is thought to possess about 1000 VSG genes, an example of mosaic gene expression. Epidemiology African trypanosomiasis is restricted to recognized tsetse fly belts. T. brucei gambiense, transmitted by the streamside tsetse Glossina palpalis and several other humid forest tsetse vectors, extends from West to Central Africa and produces a relatively chronic infection with progressive CNS involvement. T. brucei rhodesiense, transmitted by the woodland­savanna Glossina morsitans, Glossina pallidipes, and Glossina fuscipes, occurs in the eastern and southeastern savannas of Africa, with foci west of Lake Victoria. It causes a smaller number of cases but is more virulent. Bushbuck and other antelopes may serve as reservoirs of T. brucei rhodesiense, whereas humans are the principal reservoir of T. brucei gambiense. Control depends on searching for and then isolating and treating patients with the disease; controlling movement of people in and out of fly belts; using insecticides in vehicles; and instituting fly control, principally with aerial insecticides and by altering habitats. Contact with reservoir animals is difficult to control, and insect repellent is of little value against tsetse bites. TRYPANOSOMA CRUZI (BLOOD FLAGELLATE) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 The Organism Chapter 46: Medical Parasitology, Page 17 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility T. cruzi has three developmental stages: epimastigotes in the vector, trypomastigotes (in the bloodstream), and a rounded intracellular stage, the amastigote. The blood forms of T. cruzi are present during the early acute stage and at intervals thereafter in smaller numbers. They are typical other antelopes may serve as reservoirs of T. brucei rhodesiense, whereas humans are the principal reservoir of T. brucei gambiense. Control depends Access Provided by: on searching for and then isolating and treating patients with the disease; controlling movement of people in and out of fly belts; using insecticides in vehicles; and instituting fly control, principally with aerial insecticides and by altering habitats. Contact with reservoir animals is difficult to control, and insect repellent is of little value against tsetse bites. TRYPANOSOMA CRUZI (BLOOD FLAGELLATE) The Organism T. cruzi has three developmental stages: epimastigotes in the vector, trypomastigotes (in the bloodstream), and a rounded intracellular stage, the amastigote. The blood forms of T. cruzi are present during the early acute stage and at intervals thereafter in smaller numbers. They are typical trypomastigotes with a large, rounded terminal kinetoplast in stained preparations, but they are difficult to morphologically distinguish from African trypanosomes. The tissue forms, which are most common in heart muscle, liver, and brain, develop as amastigotes that multiply to form an intracellular colony after invasion of the host cell or phagocytosis of the parasite (Figure 46­5). FIGURE 46­5 T. cruzi amastigote colonies (arrows) in heart muscle. Amastigotes are 1–3 μm in diameter in tissue sections. (Used with permission from Sullivan J: A Color Atlas of Parasitology, 8th ed. 2009.) Diagram of an amastigote with the characteristic “dot” (nucleus) and “dash” (kinetoplast). Pathology and Pathogenesis Infective forms of T. cruzi do not pass to humans by triatomine bug bites (which is the mode of entry of the nonpathogenic Trypanosoma rangeli); rather, they are introduced when infected bug feces are rubbed into the conjunctiva, the bite site, or a break in the skin. At the site of T. cruzi entry, there may be a subcutaneous inflammatory nodule or chagoma. Unilateral swelling of the eyelids (Romaña’s sign) is characteristic at onset, especially in children. The primary lesion is accompanied by fever, acute regional lymphadenitis, and dissemination to blood and tissues. Acute Chagas disease can also be asymptomatic. In the chronic stage, the most serious complication is chagasic cardiomyopathy associated with fibrosis in response to the presence of intracellular parasites in heart tissue. When fibrosis occurs in the conduction system of the heart, arrhythmias can develop that can lead to sudden death. Invasion or toxic destruction of nerve plexuses in the alimentary tract walls leads to megaesophagus and megacolon, especially in Brazilian Chagas disease. Megaesophagus and megacolon are absent in Colombian, Venezuelan, and Central American Chagas disease. T. rangeli of South and Central America infects humans without causing disease and must therefore be carefully distinguished from the pathogenic species. Epidemiology American trypanosomiasis (Chagas disease) is especially important in Central and South America, although infection of animals extends much more widely—for example, to Maryland and southern California. Autochthonous transmission of human Chagas disease has now been well documented in Texas and possibly elsewhere in the southwestern United States (Garcia et al, 2015). Drug treatment with benznidazole or nifurtimox is effective at the Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 acute stages Chapter of the illness, 46: Medical or early in the chronic phase, but does not improve the clinical outcome once the progression of heart disease Page Parasitology, begins. 18Since / 54 treatment ©2024 options McGraw areAll Hill. limited Rightsit Reserved. is particularly important Terms of Useto control Privacythe vectors Policy with residual Notice insecticides and habitat modification, such as replacement Accessibility of mud­brick (adobe) houses with thatched roofs where the insects live, and to avoid contact with animal reservoirs. Chagas disease occurs largely among people in poor economic circumstances. An estimated 7–8 million people harbor the parasite, and many of these individuals sustain heart  Access Provided by: Epidemiology American trypanosomiasis (Chagas disease) is especially important in Central and South America, although infection of animals extends much more widely—for example, to Maryland and southern California. Autochthonous transmission of human Chagas disease has now been well documented in Texas and possibly elsewhere in the southwestern United States (Garcia et al, 2015). Drug treatment with benznidazole or nifurtimox is effective at the acute stages of the illness, or early in the chronic phase, but does not improve the clinical outcome once the progression of heart disease begins. Since treatment options are limited it is particularly important to control the vectors with residual insecticides and habitat modification, such as replacement of mud­brick (adobe) houses with thatched roofs where the insects live, and to avoid contact with animal reservoirs. Chagas disease occurs largely among people in poor economic circumstances. An estimated 7–8 million people harbor the parasite, and many of these individuals sustain heart damage, with the result that their ability to work and their life expectancy are sharply reduced. LEISHMANIA SPECIES (BLOOD FLAGELLATES) The Organisms The sand fly transmits the infective promastigotes during a bite. The promastigotes rapidly change to amastigotes after phagocytosis by macrophages or monocytes, and then multiply, filling the cytoplasm of the cell. The infected cells burst, and the released parasites are again phagocytosed. This process is repeated, producing a cutaneous lesion or visceral infection depending on the species of parasite and the host response. The amastigotes are ovoid and approximately 2–3 μm in size. The nucleus and a dark­staining, rod­like kinetoplast can be seen as a “dot” and a “dash.” The genus Leishmania, widely distributed in nature, has a number of species that are nearly identical morphologically. Clinical characteristics of the disease are traditional differentiating characteristics, but many exceptions are now recognized. The different leishmanias present a range of clinical and epidemiologic characteristics that, for convenience only, are combined under three clinical groupings: (1) cutaneous leishmaniasis (Oriental sore, Baghdad boil, wet cutaneous sore, dry cutaneous sore, chiclero ulcer, uta, and other names), (2) mucocutaneous leishmaniasis (espundia), and (3) visceral leishmaniasis (kala­azar—Hindi for black fever). There are strain differences in virulence, tissue tropism, and biologic and epidemiologic characteristics, as well as in the serologic and biochemical criteria. Some species can induce several disease syndromes (eg, visceral leishmaniasis from organisms of cutaneous leishmaniasis or cutaneous leishmaniasis from organisms of visceral leishmaniasis). Similarly, the same clinical condition can be caused by different agents. Pathology and Pathogenesis Leishmania tropica, Leishmania major, Leishmania mexicana, Leishmania braziliensis, and other cutaneous forms induce a dermal lesion at the site of inoculation by the sand fly (cutaneous leishmaniasis, Oriental sore, Delhi boil, etc). The dermal layers are first affected, with cellular infiltration and proliferation of amastigotes intracellularly and spreading extracellularly, until the infection penetrates the epidermis and causes ulceration. Satellite lesions may be found (hypersensitivity or recidivans type of cutaneous leishmaniasis) that contain few or no parasites, do not readily respond to treatment, and induce a strong granulomatous scarring reaction. In Venezuela, a cutaneous disseminating form, caused by L. mexicana pifanoi, is known. In Ethiopia, a form known as Leishmania aethiopica causes a similar nonulcerating, blistering, spreading cutaneous leishmaniasis. Both forms are typically anergic and nonreactive to skin test antigen and contain large numbers of parasites in the dermal blisters. L. braziliensis braziliensis causes mucocutaneous or nasopharyngeal leishmaniasis in Amazonian South America. It is known by many local names. The lesions are slow growing but extensive (sometimes 5–10 cm). From these sites, migration appears to occur rapidly to the nasopharyngeal or palatine mucosal surfaces, where no further growth may take place for years. After months to more than 20 years, relentless erosion may develop, destroying the nasal septum and surrounding regions. In some instances, death occurs from asphyxiation due to blockage of the trachea, starvation, or respiratory infection. This is the classic clinical picture of espundia (Figure 46­6), most commonly found in the Amazon basin. At high altitudes in Peru, the clinical features (uta) resemble those of Oriental sore. L. braziliensis guyanensis infection frequently spreads along lymphatic routes, where it appears as a linear chain of nonulcerating lesions. L. mexicana infection is more typically confined to a single, indolent, ulcerative lesion that heals in about 1 year, leaving a characteristic depressed circular scar. In Mexico and Guatemala, the ears are frequently involved (chiclero ulcer), usually with a cartilage­attacking infection without ulceration and with few parasites. FIGURE 46­6 A patient with espundia caused by L. braziliensis. (Reproduced with permission from WHO/TDR image library.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 19 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility cartilage­attacking infection without ulceration and with few parasites. Access Provided by: FIGURE 46­6 A patient with espundia caused by L. braziliensis. (Reproduced with permission from WHO/TDR image library.) Leishmania donovani, which causes visceral leishmaniasis or kala­azar, spreads from the site of inoculation to multiply in reticuloendothelial cells, especially macrophages in spleen, liver, lymph nodes, and bone marrow (Figure 46­7). This is accompanied by marked hyperplasia of the spleen. Progressive emaciation is accompanied by growing weakness. There is irregular fever, sometimes hectic. Untreated cases with symptoms of kala­azar usually are fatal. Some forms, especially in India, develop a postcure florid cutaneous resurgence, with abundant parasites in cutaneous vesicles, 1–2 years later (post­kala­azar dermal leishmanoid). FIGURE 46­7 Leishmania donovani amastigotes (arrows) from a liver biopsy. (Courtesy of Pathology, UCSF.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 20 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility years later (post­kala­azar dermal leishmanoid). Access Provided by: FIGURE 46­7 Leishmania donovani amastigotes (arrows) from a liver biopsy. (Courtesy of Pathology, UCSF.) Epidemiology It is estimated that the prevalence of leishmaniasis is approximately 4.8 million worldwide (GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017) and 20,000–30,000 deaths occur annually (WHO Leishmaniasis, 2018). Oriental sore occurs mostly in the Mediterranean region, North Africa, and the Middle and Near East. The “wet” type, caused by L. major, is rural, and burrowing rodents are the main reservoir; the “dry” type, caused by L. tropica, is urban, and humans are presumably the only reservoir. For L. braziliensis, there are a number of wild animal hosts, but apparently there are no domestic animal reservoirs. Sand fly vectors are involved in all forms. L. donovani is found focally in most tropical and subtropical countries. Its local distribution is related to the prevalence of specific sand fly vectors. In the Mediterranean littoral and in middle Asia and South America, domestic and wild canids are reservoirs, and in the Sudan, various wild carnivores and rodents are reservoirs of endemic kala­azar. Control is aimed at destroying breeding places and dogs, where appropriate, and protecting people from sand fly bites. ENTAMOEBA HISTOLYTICA (TISSUE AMEBA)—SEE INTESTINAL PROTOZOAN INFECTIONS SECTION NAEGLERIA FOWLERI, ACANTHAMOEBA CASTELLANII, AND BALAMUTHIA MANDRILLARIS (FREE­LIVING AMEBAE) The Organisms Primary amebic meningoencephalitis (PAM) and granulomatous amebic encephalitis (GAE) occur in Europe and North America from amebic invasion of the brain. The free­living soil amebae N. fowleri, A. castellanii, B. mandrillaris, and possibly species of Hartmannella have been implicated. Most cases are associated with individuals who were swimming and diving in warm, soil­contaminated freshwater (eg, ponds, rivers, or hot springs). Individuals have also become infected after irrigating their nasal sinuses with contaminated water using a neti pot. Pathology and Pathogenesis The amebae, primarily N. fowleri, enter via the nose and the cribriform plate of the ethmoid bone, passing directly into brain tissue, where they rapidly form nests of amebae that cause extensive hemorrhage and damage, chiefly in the basilar portions of the cerebrum and the cerebellum (Figure 46­8). FIGURE 46­8 Dark areas of the cerebellum are regions of necrosis caused by N. fowleri amebae. (Courtesy of Pathology, UCSF.) Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 21 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility form nests of amebae that cause extensive hemorrhage and damage, chiefly in the basilar portions of the cerebrum and the cerebellum (Figure 46­8). Access Provided by: FIGURE 46­8 Dark areas of the cerebellum are regions of necrosis caused by N. fowleri amebae. (Courtesy of Pathology, UCSF.) The incubation period is from 1 to 14 days; early symptoms include headache, fever, lethargy, rhinitis, nausea, vomiting, and disorientation and resemble acute bacterial meningitis. In most cases, patients become comatose and die within a week. The key to diagnosis is clinical suspicion based on recent history of swimming or diving in warm waters. Entry of Acanthamoeba into the CNS occurs from skin ulcers or traumatic penetration, such as keratitis from puncture of the corneal surface or ulceration from contaminated saline used with contact lenses. GAE is caused by Acanthamoeba and Balamuthia and is often associated with immunocompromised individuals. Infection of the CNS from the skin lesion may occur weeks or months later. It is termed GAE to distinguish it from the explosive, rapid brain infection from Naegleria (PAM). Treatment with amphotericin B has been successful in a few cases, chiefly in the rare instances when diagnosis can be made quickly. PLASMODIUM SPECIES (BLOOD SPOROZOA) Malaria is the number one killer of all the parasitic diseases. More than 90% of the deaths worldwide occur in sub­Saharan Africa. In 2016, it was estimated that there were 216 million malaria cases and an estimated 445,000 deaths (WHO World Malaria Report, 2017). The Organisms There are four main species of Plasmodium that cause malaria in humans: Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, and Plasmodium ovale. Plasmodium knowlesi, which normally infects macaques, is known to cause zoonotic malaria in Southeast Asia. The two most common species are P. vivax and P. falciparum, with falciparum being the most pathogenic of all. Transmission to humans is by the bloodsucking bite of female Anopheles mosquitoes (Figure 46­9). The morphology and other characteristics of these species are summarized in Table 46­6 and illustrated in Figures 46­10 and 46­11 A–C. FIGURE 46­9 Life cycle of malaria parasites. Continuous cycling or delayed multiplication in the liver may cause periodic relapse over several years (1–2 years in P. ovale, 3–5 years in P. vivax). Relapse does not occur with P. falciparum, although a long prepatent period may occur, resulting in initial symptoms appearing up to 6 months or more after exposure. Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 Chapter 46: Medical Parasitology, Page 22 / 54 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility FIGURE 46­9 Access Provided by: Life cycle of malaria parasites. Continuous cycling or delayed multiplication in the liver may cause periodic relapse over several years (1–2 years in P. ovale, 3–5 years in P. vivax). Relapse does not occur with P. falciparum, although a long prepatent period may occur, resulting in initial symptoms appearing up to 6 months or more after exposure. TABLE 46­6 Some Characteristic Features of the Malarial Parasites of Humans (Romanowsky­Stained Preparations) Plasmodium vivax Plasmodium falciparum Plasmodium malariae Plasmodium ovale Parasitized Enlarged, pale. Fine stippling Not enlarged. Coarse stippling (Maurer’s Not enlarged. No stippling Enlarged, pale. Schüffner red cells (Schüffner dots). Primarily clefts). Invades all red cells regardless of (except with special stains). dots conspicuous. Cells invades reticulocytes, young age Primarily invades older red often oval, fimbriated, or red cells cells crenated Level of Up to 30,000/μL of blood May exceed 200,000/μL; commonly Fewer than 10,000/μL Fewer than 10,000/μL usual 50,000/μL maximum parasitemia Ring stage Large rings (1/3–1/2 red cell Small rings (1/5 red cell diameter). Often Large rings (1/3 red cell Large rings (1/3 red cell trophozoites diameter). Usually one two granules; multiple infections diameter). Usually one diameter). Usually one chromatin granule; ring common; ring delicate, may adhere to chromatin granule; ring chromatin granule; ring delicate red cells thick thick Pigment in Fine; light brown; scattered Coarse; black; few clumps Coarse; dark brown; Coarse; dark yellow­brown; developing scattered clumps; abundant scattered trophozoites Older Very pleomorphic Compact and roundeda Occasional band forms Compact and rounded trophozoites Mature More than 12 merozoites (14– Usually more than 12 merozoites (8–32). Fewer than 12 large Fewer than 12 large schizonts 24) Very rare in peripheral blooda merozoites (6–12). Often in merozoites (6–12). Often in (segmenters) rosette rosette Gametocytes Round or oval Crescentic Round or oval Round or oval Distribution All forms Only rings and crescents (gametocytes)a All forms All forms Downloaded 2024­8­3 12:48 A Your IP is 110.170.245.233 in peripheral Chapter 46: Medical Parasitology, Page 23 / 54 blood ©2024 McGraw Hill. All Rights Reserved. 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